ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.507G>A (p.Gln169=) (rs876660937)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220906 SCV000278755 likely pathogenic Hereditary cancer-predisposing syndrome 2019-05-08 criteria provided, single submitter clinical testing Functionally-validated splicing mutation;Last nucleotide of exon;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000463637 SCV000547332 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-15 criteria provided, single submitter clinical testing This sequence change affects codon 169 of the BRIP1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRIP1 protein. This variant also falls at the last nucleotide of exon 5 of the BRIP1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in families affected with ovarian and/or breast cancer (PMID: 29368626). ClinVar contains an entry for this variant (Variation ID: 234221). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 29368626). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000486318 SCV000569863 uncertain significance not provided 2016-09-06 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.507G>A at the DNA level. Although this variant is silent at the coding level, preserving a Glutamine at codon 169, it is predicted to cause abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRIP1 c.507G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The nucleotide which is altered, a guanine (G) at base 507, is conserved across species. Based on currently available information, it is unclear whether BRIP1 c.507G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000220906 SCV000689398 likely pathogenic Hereditary cancer-predisposing syndrome 2020-03-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.